Kifor I, Williams G H, Vickers M A, Sullivan M P, Jodbert P, Dluhy R G
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
J Urol. 1997 May;157(5):1920-5.
Although Angiotensin II (Ang II) is a major modulator of regional blood flow in the extracavernosal segments of the vascular bed, its role in erectile function is unknown. The corpus cavernosum penis is a modified vascular tissue that contains endothelial and smooth muscle cells. In other segments of the vascular bed, these cell types produce Ang II. Therefore, we explored the presence and function of an Ang II producing paracrine system in the corpus cavernosum.
The angiotensin content of the human corpus cavernosum was measured by radioimmunoassay. The distribution pattern of Ang II containing cells within the corpus cavernosum was assessed by an immunohistochemical technique, and the rate of its secretion was determined by superfusion. The effects of Ang II and its antagonist, losartan, on intracavernosal pressure were determined under in vivo conditions, in anesthetized dogs.
Human corpus cavernosum contained 1178 +/- 223 (SEM) fmol Ang II, 528 +/- 171 fmol Ang I, 475 +/- 67 fmol des-asp-Ang I, and 1897 +/- 371 fmol des-asp-Ang II/gm. tissue (n = 4). Ang II was found mainly in endothelial cells lining blood vessels and smooth muscle bundles within the corpus cavernosum. Superfused cavernosal tissue secreted immuno-reactive Ang II (Ang II(ir)) at a rate of 57 +/- 36.5 fmol Ang II(ir)/gm. tissue/minute (n = 10). The amount of Ang II released per gram of tissue in an hour was 3-fold greater than the Ang II content/gm. tissue, suggesting a local production of Ang II. Papaverine and prostaglandin E1 suppressed Ang II secretion significantly (p <0.001, p = 0.013). The responsiveness to inhibition was a function of the initial rate of Ang II secretion. Tissue samples with a high rate of secretion were less responsive to the inhibitors than tissue that secreted small amounts of Ang II (n = 6). In anesthetized dogs, intra-cavernosal injection of Ang II terminated spontaneous erections, while losartan increased the intracavernosal pressure in a dose dependent manner up to the mean arterial pressure (n = 4).
The corpus cavernosum produces and secretes physiologically relevant amounts of Ang II. The rate of Ang II secretion can be modulated by pharmacologic agents that regulate cytosolic calcium levels and are used clinically to treat erectile dysfunction. Intracavernosal injection of Ang II causes contraction of cavernosal smooth muscle and terminates spontaneous erection in anesthetized dog, while administration of an Ang II receptor antagonist results in smooth muscle relaxation and thus erection.
尽管血管紧张素II（Ang II）是血管床海绵体段以外区域血流的主要调节因子，但其在勃起功能中的作用尚不清楚。阴茎海绵体是一种特殊的血管组织，包含内皮细胞和平滑肌细胞。在血管床的其他部位，这些细胞类型可产生Ang II。因此，我们探讨了阴茎海绵体内产生Ang II的旁分泌系统的存在及其功能。
采用放射免疫分析法测定人阴茎海绵体中的血管紧张素含量。通过免疫组化技术评估阴茎海绵体内含Ang II细胞的分布模式，并通过灌流法测定其分泌速率。在麻醉犬的体内条件下，测定Ang II及其拮抗剂氯沙坦对海绵体内压的影响。
人阴茎海绵体每克组织含1178±223（SEM）fmol Ang II、528±171 fmol Ang I、475±67 fmol去天门冬氨酸-Ang I和1897±371 fmol去天门冬氨酸-Ang II（n = 4）。Ang II主要存在于阴茎海绵体内血管内皮细胞和平滑肌束中。灌流的海绵体组织以57±36.5 fmol Ang II（ir）/克组织/分钟的速率分泌免疫反应性Ang II（Ang II（ir））（n = 10）。每克组织每小时释放的Ang II量比每克组织中的Ang II含量高3倍，提示Ang II为局部产生。罂粟碱和前列腺素E1可显著抑制Ang II分泌（p<0.001，p = 0.013）。抑制反应性是Ang II分泌初始速率的函数。分泌速率高的组织样本对抑制剂的反应性低于分泌少量Ang II的组织（n = 6）。在麻醉犬中，海绵体内注射Ang II可终止自发性勃起，而氯沙坦则以剂量依赖性方式使海绵体内压升高至平均动脉压（n = 4）。
阴茎海绵体可产生并分泌具有生理活性的Ang II。Ang II的分泌速率可被调节细胞内钙水平且临床上用于治疗勃起功能障碍的药物所调节。海绵体内注射Ang II可导致海绵体平滑肌收缩并终止麻醉犬的自发性勃起，而给予Ang II受体拮抗剂则可导致平滑肌松弛从而引起勃起。
